Enhancement of the avoidance-suppressing effects of neuroleptic agents after repeated administration: changes in the discriminated avoidance response in rats.

Changes in the discriminated avoidance response of the rat after repeated administration of N-(1-benzyl-3-pyrrolidinyl)-5-chloro-2-methoxy-4-methylaminobenzamide (YM-08050; 0.01 mg/kg SC) and N-(1-benzyl-3-pyrrolidinyl)-5-chloro-methoxy-4-dimethylaminobenzamide (YM-08051; 0.1 mag/kg SC), potent neuroleptic agents of the benzamide derivative type, were investigated. The avoidance-suppressing effects of YM-08050 and YM-08051, i.e., decreases in the response (lever-pressing) and avoidance rates, were enhanced after repeated administration. The changes in behavior were more marked in animals exposed to the avoidance situation during the period of the drug effect than those given the drugs after the termination of each avoidance session. The enhancing effect, once it had appeared, remained even after 1 week. The present results suggest that the avoidance-suppressing effects of YM-08050 and YM-08051 are enhanced after repeated administration, and that the effect is strongly dependent on the drug experience of the experimental animals and on the experimental situation to which the animals are exposed during the period of the drug effect.